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Autoantibodies to mitochondrial antigens are characteristic of the autoimmune liver disease, primary biliary cirrhosis (PBC), but the precise antigenic determinants recognized by these antibodies have not been defined. Recently, our laboratory identified a 1370 basepair rat liver cDNA clone that coded for a polypeptide recognized specifically by sera from patients with PBC, but not by sera from patients with other forms of liver disease. This recombinant protein was identified as the 74kDa M2 mitochondrial inner membrane autoantigen, now known to be dihydrolipoamide acetyltransferase. In the present study, we have identified a 603 base-pair fragment which codes for a polypeptide containing all of the autoreactivity of the original clone. In addition, based on hydrophobicity/hydrophilicity plots of the amino acid sequence of this polypeptide segment, several peptides were synthesized and tested for reactivity by an …